R & D
Articles, Conference Presentations and PatentsA synopsis of our articles, conference presentations and patents.
Articles
Brazilian green propolis suppresses acetaminophen-induced hepatocellular necrosis by modulating inflammation-related factors in ratsJ Toxicol Pathol. 2018 Oct;31(4):275-282. doi: 10.1293/tox.2018-0027. Epub 2018 Jul 1.
Propolis is a resin-like material produced by honey bees from bud exudates and sap of plants and their own secretions. An ethanol extract of Brazilian green propolis (EEBGP) contains prenylated phenylpropanoids and flavonoids and has antioxidative and anti-inflammatory effects. Acetaminophen (N-acetyl-p-aminophenol; APAP) is a typical hepatotoxic drug, and APAP-treated rats are widely used as a model of drug-induced liver injury. Oxidative stress and inflammatory reactions cause APAP-induced hepatocellular necrosis and are also related to expansion of the lesion. In the present study, we investigated the preventive effects of EEBGP on APAP-induced hepatocellular necrosis in rats and the protective mechanism including the expression of antioxidative enzyme genes and inflammation-related genes. A histological analysis revealed that administration 0.3% EEBGP in the diet for seven days reduced centrilobular hepatocellular necrosis with inflammatory cell infiltration induced by oral administration of APAP (800 mg/kg) and significantly reduced the area of necrosis. EEBGP administration did not significantly change the mRNA expression levels of antioxidant enzyme genes in the liver of APAP-treated rats but decreased the mRNA expression of cytokines including Il10 and Il1b, with a significant difference in Il10 expression. In addition, the decrease in the mRNA levels of the Il1b and Il10 genes significantly correlated with the decrease in the percentage of hepatocellular necrosis. These findings suggest that EEBGP could suppress APAP-induced hepatocellular necrosis by modulating cytokine expression.
Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in ratsJ Toxicol Pathol. 2018 Oct;31(4):267-274. doi: 10.1293/tox.2018-0009. Epub 2018 Jun 16.
It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (N-acetyl-p-aminophenol; APAP), were examined in rats reared under different feeding conditions: ad libitum feeding, 16-h fasting, and food restriction (fed 70% of the average intake of ad libitum feeding for 10 days) conditions. The rats under food restriction conditions as well as fasted rats showed significantly higher expression of Cyp2e1, the gene encoding the enzyme that metabolizes APAP to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). They also had lower levels of liver total glutathione, which detoxifies NAPQI. In contrast, the gene expression of UDP-glucuronosyltransferase 1A6 (Ugt1a6), sulfotransferase 1A1 (Sult1a1), and glutathione S-transferase M1 (Gstm1) was not affected by food restriction or fasting. When APAP was administered (800 mg/kg), histopathological changes were not observed in rats fed ad libitum, while hepatocellular necrosis was observed in most of the rats treated with APAP after fasting or food restriction. Taken together, these results suggest that not only fasting but also food restriction exacerbate APAP-induced acute liver injury, probably by the induction of CYP2E1 and the reduction of liver glutathione contents, in rodents.
A Double-blinded, Placebo-controlled, Crossover Trial of Low Dose Extract of Aquilaria sp (Thymelaeaceae) LeavesJpn Pharmacol Ther 2017, 45(1): 113-120
Objectives We have revealed the efficacy and safety of Aquilaria subintegra (agarwood)leave extract on constipation-related symptoms. To evaluate the effect of low dosage of agarwood leaves extract, two clinical trials were performed in this study.
Methods Clinical trial-1. We conducted a double-blinded, placebo-controlled, crossover trial in seventeen healthy volunteers-(ages 20 to 65 years old)with mild constipation. For the trial, we prepared a tablet containing a mixed powder of 75 mg agarwood leaves- extract and 75 mg dextrin. The subjects ingested placebo or 150 mg of the agarwood leave extrac(t 2 tablets daily) for 4 weeks. Clinical trial-2. We conducted the trial, which methods were the same as clinical trial-1, with twofold dosage of the agarwood leave extract. Fifteen healthy volunteers with mild constipation were participated in this trial. In each trial, the primary endpoints were changes in self-reported stool smell and the frequency of defecation.
Results Clinical trial-1. No significant differences were indicated in any endpoints. And any clinically critical adverse events were not observed in this trial. Clinical trial-2. Significant improvements were indicated in the primary endpoints, the stool volume and the total frequency of defecation. Especially, the stool smell was improved at first week in the intake period of agarwood leaves extract tablets. In addition, any clinically critical adverse events were not observed during the trial.
Conclusions Present results suggested that the intake of 300 mg of the agarwood leave extract serves to relieve constipation without adverse effects.
Quantitative analysis of apisin, a major protein unique to royal jelly.Evid Based Complement Alternat Med., 2016. 5040528
Apisin, a protein that is unique to royal jelly (RJ), is known to compose the greater part of the RJ proteins and to exist as a heterooligomer containing major royal jelly protein 1 and apisimin. However, few reports on the methods for quantifying apisin have been published. Thus, we attempted to quantify apisin using HPLC, a widely used analytical technique, as described below. Isoelectric precipitation and size-exclusion chromatography were used to obtain the purified protein, which was identified as apisin by SDS-PAGE and LC-MS analyses. The purified apisin was lyophilized and then used to generate a calibration curve to quantify apisin in RJ. The apisin content was fairly constant (i.e., 3.93 to 4.67 w/w%) in natural RJ. This study is the first to describe a simple, standardized method for quantifying apisin using HPLC and suggests that apisin can be used as a benchmark for future evaluations of RJ quality.
Discovery of a novel diterpene in Brown Propolis from the state of Parana, Brazil. Nat Prod Commun., 2016 Feb; 11(2): pp201-205.
Propolis is a resinous substance collected by honeybees from certain plant sources. The components of propolis depend on the vegetation of the area in which apiculture is practiced. In Brazil, there are several types of propolis including 'green,' 'red' and 'brown'. Brazilian brown propolis from the state of Parana characteristically includes diterpenes, and we discovered a novel clerodane diterpene, rel-(5S,6S,8R,9R,10S,18R,19S)-18,19-epoxy-2-oxocleroda-3,12(E),14- triene-6,18,19-triol 18,19-diacetate 6-benzoate (3) and five known diterpenes (1, 2, 4, 5 and 6). The chemical structure of the novel diterpene 3 was determined using 1D- and 2D-NMR spectroscopic analyses. Furthermore, the activities of the isolated diterpenes on growth inhibition of several human cancer cell lines (LNCaP, MCF-7, DLD-1 and A549) were evaluated in vitro; diterpene 3 exhibited a potent inhibition of cell growth, and its activity was approximately 15 times higher than that of the other diterpenes.
10-hydroxy-2-decenoic acid (decene acid), a characteristic fatty acid in royal jelly extends the lifespan of the nematode Caenorhabditis elegans through dietary restriction and TOR signaling.Journal of Aging Research 2015, Volume 2015, Article ID 425261, Epub Jan 23
Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling.We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.
A Double-blinded, Placebo-controlled, Crossover Trial and Open-label Safety Trials of Extract of Aquilaria sp(Thymelaeaceae)Leaves. Yakuri to Chiryo (Jpn Pharmacol Ther) 2015, 43(2): 209-229
Objectives We investigated whether or not intake of an extract of Aquilaria crassna(agarwood)leaves ameliorates constipation—related symptoms in healthy volunteers with mild constipation, and then we also assessed clinical events produced by subchronic oral administration or an overdose of the agarwood leave extract in healthy volunteers. We prepared a tablet containing a mixed powder of 100 mg agarwood leave extract and 100 mg dextrin for carrying out these clinical experiments.
Methods Clinical trial-1. We conducted a double-blinded, placebo-controlled, crossover trial in 64 healthy volunteers(ages 20 to 65 years old)with mild constipation. The subjects ingested placebo or 600 mg of the agarwood leave extract(6 tablets daily)for 2 weeks. The primary endpoints were changes in self-reported stool volume and the number of bowel movements. Clinical trial-2. We conducted an open-label trial with 22 volunteers(age 20 to 65 years old)in which 11 subjects had a mild constipation. The subject ingested 600 mg of the agarwood leave extract(6 tablets daily), the same dose as in the Clinical trial-1, for 12 weeks and underwent physician interviews, physical examinations, blood tests, laboratory examination, urine tests, and medical examination interviews. Clinical trial-3. We conducted an open-label trial with 22 volunteers(ages 20 to 65 years old)in which 11 subjects had a mild constipation. The subjects ingested 1800 mg(18 tablets daily)of the agarwood leave extract for 4 weeks and underwent the same examinations as in the clinical trial-2. A stool volume, the total number of bowel movements, and days with defecation were recorded using a constipation diary.
Results Clinical trial-1. Daily ingestion of 600 mg of the extract significantly increased the primary endpoints, the stool volume and the total number of bowel movements, as compared with placebo. In addition, any clinically critical adverse events were not found during the study period. Clinical trial-2. Daily ingestion of 600 mg of the agarwood leave extract did not cause clinically critical changes in any parameters in all the examinations. We observed adverse events in 9 out of 22 subjects, and 3 of them dropped out of the study. All the adverse events were thought to be unrelated with ingestion of the test food. Clinical trial-3. Daily ingestion of 1800 mg of the extract did not cause clinically critical changes in any parameters in physical examinations, blood tests, and urine tests. We observed adverse events in 19 out of 22 subjects, and 8 of them dropped out of the study. Almost all the adverse events were thought to be caused by excessive stimulation of gastrointestinal motility due to overdose.
Conclusions Present results indicate that the adequate ingestion of the Aquilaria crassna leaves extract possibly serves to relieve constipation without critical adverse reaction.
Effect of Brazilian green propolis ethanol extract on human cytochrome P450 enzyme activity in vitroJ. Agric. Food Chem., 2014 Nov; 62 (46); 11296–11302. Epub 2014 Oct 31.
Supplement-drug interaction on CYP enzyme activity is occasionally found to cause clinically adverse events, and no report on interactions of propolis is available either in vitro or clinical. In this study, we tried to estimate the risk of an interaction between an ethanol extract of Brazilian green propolis (EEP-B55) and drugs in vitro and in vivo. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were attenuated by EEP-B55 in a concentration-dependent manner, and artepillin C, kaempferide, dihydrokaempferide, isosakuranetin, and kaempferol were estimated to have potential for CYP inhibition. The IC50 values of artepillin C for each CYP were approximately 33-fold higher than its Cmax in the blood of rats after dosing with 5-fold the recommended daily intake of EEP-B55. These findings suggest that liver CYP enzyme activities are not markedly affected by artepillin C at the recommended daily intake of EEP-B55.
Artepillin C, a major component of Brazilian green propolis, produces pungent taste through the activation of TRPA1 channels.PLoS One. 2012;7(11):e48072 Epub 2012 Nov 2.
Brazilian green propolis is a popular health supplement because of its various biological properties. The ethanol extract of Brazilian green propolis (EEBP) is characteristic for its herb-like smell and unique pungent taste. However, the ingredients responsible for its pungency have not yet been identified. This study provides the first evidence that artepillin C is the main pungent ingredient in EEBP and that it potently activates human transient receptor potential ankyrin 1 (TRPA1) channels. EEBP was fractionated using column chromatography with a step gradient elution of an ethanol-water solution, and the fractions having the pungent taste were determined by sensory tests. HPLC analysis revealed that the pungent fraction was composed primarily of artepillin C, a prenylated derivative of cinnamic acid. Artepillin C was also identified as the pungent compound of EEBP by organoleptic examiners. Furthermore, the effects of artepillin C and other cinnamic acids found in EEBP on TRPA1 channels were examined by calcium imaging and plate reader-based assays in human TRPA1-expressing cells to investigate the molecular mechanisms underlying their pungent tastes. Artepillin C and baccharin activated the TRPA1 channel strongly, whereas drupanin caused a slight activation and p-coumaric acid showed no activation. Because the EC(50) values of artepillin C, baccharin, and allyl isothiocyanate were 1.8 µM, 15.5 µM, and 6.2 µM, respectively, artepillin C was more potent than the typical TRPA1 agonist allyl isothiocyanate. These findings strongly indicate that artepillin C is the main pungent ingredient in EEBP and stimulates a pungent taste by activating TRPA1 channels.
Laxative effect and mechanism of action of green propolis.BMC Complement Altern Med. 2012 Oct 22;12:192.
BACKGROUND: Brazilian green propolis is reported to have wide range of biological properties including antibacterial, anti-inflammatory, anti-influenza, and antioxidant activities. In the digestive system, a protective effect of propolis on gastric ulcer has been reported, but a laxative effect has not yet been reported. We investigated the effect and the mechanism of action of water and ethanol extracts of Brazilian green propolis. METHODS: We examined the laxative effect of propolis on stool frequency by administering orally an ethanol extract of propolis (EEP) or a water extract of propolis (WEP) at 10, 50, 100, or 500 mg/kg to normal mice. We then investigated the effects of propolis using constipation model mice induced by two types of drugs, loperamide (a μ opioid receptor agonist) and clonidine (an α-2 adrenergic receptor agonist). We also investigated the effects of WEP on gastrointestinal transit and contractional tension of the ileum to uncover the mechanism of action of WEP. RESULTS: Treatment with WEP, but not with EEP, significantly increased the weight of stools (p<0.01 at 500 mg/kg). WEP treatment significantly restored stool frequency and stool weight in clonidine-induced constipation model mice, but not in loperamide-induced constipation model mice. WEP treatment did not affect gastro-intestinal transit, but significantly increased the contractional tension of the isolated ileum of guinea pigs. This increase was inhibited by an acetylcholine receptor antagonist (atropine), but not by a 5-HT receptor antagonist (GR113808). CONCLUSION: These findings indicate that WEP has laxative effects both in normal mice and in clonidine-induced constipation model mice. The laxative effects of WEP might be mediated by increased contractional tension of the ileum exerted at least in part via activation of an acetylcholine receptor.
Ethanol extract of Brazilian red propolis increases ABCA1 expression and promotes cholesterol efflux from THP-1 macrophages.Phytomedicine. 2012 Mar 15;19(5):383-8. Epub 2012 Feb 2.
The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expression would be beneficial for the prevention and therapy of atherosclerosis. In the present study, we studied the effects of ethanolic extracts of Brazilian red propolis (EERP) on ABCA1 expression and cholesterol efflux in THP-1 macrophages. EERP enhanced PPARγ and liver X receptor (LXR) transcriptional activity at 5-15μg/ml, which was associated with upregulation of PPARγ and LXRα expression. It was also found that EERP increase the activity of the ABCA1 promoter, which is positively regulated by LXR. Consistent with these findings, treatment with EERP increased both mRNA and protein expression of ABCA1. Finally, EERP upregulated ApoA-I-mediated cholesterol efflux. Our results showed that EERP promote ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression via induction of PPARγ/LXR
Anti-influenza effect of propolis.Food Style 21: December 2011
We examined the survival improving action of Brazilian green propolis on MDCK cells infected with influenza virus A/WSN/33 (H1N1 type) and found that water extracts of propolis had a cell protective effect. The component 3,4-dicaffeoylquinic acid (3,4-diCQA) showed the strongest effect. Further, the results indicated that the observed anti-influenza effect was due to increased resistance of the cells as the viral RNA content per cell in the treated group was about the same as in the control group.
Next, we examined the effect of water extracts and ethanol extracts of propolis on survival of female Balb/c mice that developed influenza after intranasal inoculation of A/WSN/33 (to which the mice had been conditioned). Water extracts and ethanol extracts of propolis and their component 3,4-diCQA suppressed reduction of survival through their anti-influenza activity although the effect was not as strong as with Tamiflu®. Further, extracts containing the component 3,4-diCQA tended to lower viral mRNA expression levels in the lung while simultaneously increasing the expression level of mouse TRAIL significantly. From the fact that the TRAIL has influenza virus clearance action, it is believed that 3,4-diCQA acts via TRAIL.
It thus became clear that Brazilian green propolis certainly had anti-influenza effect and that the mechanism of this effect was not through direct action on the virus but through enhancement of a defense mechanism that the living body already had.
Pungent component of Brazilian propolisFood Style 21: November 2011
Brazilian green propolis has a fresh forest (herb-like) smell and a pungent taste that irritates parts up to the back of the throat. The components that cause this pungency have not been identified so far. Alcohol extract of propolis was eluted from a reverse-phase ODS column sequentially with a 30% to 100% step-wise ethanol concentration gradient. Organoleptic testing of each fraction showed that the pungent component was artepillin C. The concentration at which one started to taste the pungency was 5 mg /50 mL (dissolved in 1 mL ethanol and the volume adjusted to 50 mL with purified water).
3,4-Dicaffeoylquinic acid, a major constituent of Brazilian propolis, increases TRAIL expression and extends the lifetimes of mice infected with the influenza A virus. Evid Based Complement Alternat Med. 2012:946867. Epub 2011 Aug 25.
Brazilian green propolis water extract (PWE) and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against the influenza A virus (IAV) without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.
Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.PLoS One. 2011;6(8):e23527. Epub 2011 Aug 9.
BACKGROUND: One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.
PRINCIPAL FINDINGS: We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.
CONCLUSIONS/SIGNIFICANCE: These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process.
Caffeoylquinic acids are major constituents with potent anti-influenza effects in Brazilian green propolis water extract.Evid Based Complement Alternat Med. 2011:254914. Epub 2011 Mar 1.
Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.
Effect of a Glycoprotein (Apisin) in Royal Jelly on Proliferation and Differentiation in Skin Fibroblast and Osteoblastic CellsNippon Shokuhin Kagaku Kogaku Kaishi Vol.58, No.3, 121-126 (2011)
The aim of the present study was to quantitatively examine the growth-promoting effect and collagen production promoting effect of apisin, the main protein in royal jelly, on a human skin fibroblast cell line. Its differentiation promoting action on an osteoblast-like mouse cell line was also studied qualitatively and quantitatively. The following findings were made.
(1) Apisin promoted proliferation of the human skin fibroblast cell line NB1RGB and showed a tendency to promote collagen production by these cells.
(2) Apisin promoted calcium deposition and hydroxyapatite production, both of which are indices of differentiation, when it was added along with a differentiation inducer to the mouse osteoblast-like cell line MC3T3-E1.
Brazilian red propolis ethanol extracts promote adipocyte differentiation through activation of PPARγPhytomedicine. 2010 Oct;17(12):974-9. Epub 2010 Apr 10.
AIM OF THE STUDY: The aim of present study was to investigate the effects of ethanolic extracts of red propolis (EERP) on adipogenesis and evaluate the molecular basis for their anti-obesity effects.
MATERIALS AND METHODS: We tested whether EERP alone could induce differentiation of 3T3-L1 cells, regulate the expression of adipocyte-specific genes and reverse inhibitory effects of TNF-α on their differentiation. Next, we performed a luciferase reporter gene assay to test whether EERP could enhance transcriptional activities of PPARγ and adiponectin promoter activities.
RESULTS: EERP strongly induced differentiation of 3T3-L1 preadipocytes into adipocytes, and enhanced the PPARγ transcriptional activity and adiponectin promoter activity. In addition, EERP attenuated the inhibitory effect of TNF-α on adipocyte differentiation and adiponectin production in mature adipocytes.
CONCLUSION: The present study indicates that EERP enhance differentiation of 3T3-L1 adipocytes in part by its potency of PPARγ activation and are capable of reversing inhibitory effects of TNF-α on adipocyte differentiation and adiponectin expression. These results suggest the value of EERP as a diet supplement for prevention and treatment of obesity and obesity-associated disorders.
Conference Presentations
Study on antigenic cross-reactivity of royal jelly with common allergens
〇Taketoshi Hata1, Tomoko Takahashi2, Mariko Seishima2, Kenji Ichihara1
(1API Co., Ltd., 2Gifu University)
Studies on the antidepressant-like effect of royal jelly in an unpredictable chronic mild stress rodent model of depression (3)
〇Noriyuki Iegaki 1, Yukio Narita 1, Noriko Hattori 1, Yoko Hirata 2, Kenji Ichihara 1
(1API Co., Ltd., 2Gifu University)
Antimicrobial activity of Brazilian propolis against oral bacteria
〇Tomomi Morimoto 1, Shigemi Tazawa 1, Kaori Tanaka 2, Kenji Ichihara 1
(1API Co., Ltd., 2Gifu University)
9th Gifu Pharmaceutical University Lectures on Functional Health Foods, Gifu, December 1, 2018.
Basic research of Brazilian propolis: major constituents and in vitro anti-tumor activities
〇Taichi Mitsui, Shigemi Tazawa, Sho Hotta, Kenji Kato, Kenji Ichihara
Nagaragawa Research Center, API Co., Ltd.
2018.10.11-16 Apiquality & Apimedica 2018 The XI-th Congress of the Romanian Society of Apitherapy (Sibiu, Romania)
Atopic dermatitis patients possibly associated with cross-reactive antibodies to royal jelly.
〇Taketoshi Hata1, Takako Furusawa-Horie1, Yasuko Arai1, Tomoko Takahashi2,
Kenji Ichihara1, Mariko Seishima2
1 Nagaragawa Research Center, API Co., Ltd.
2 Department of Dermatology, Gifu University Graduate School of Medicine
2018.6.13-15 13th Meeting of the German-Japanese Society of Dermatology (Munich, Germany)
Neuroprotective activity of green Brazilian propolis in vitro 〇Madoka Takashima 1,2, Kenji Ichihara 1, Yoko Hirata 2 (1API Co., Ltd., 2Gifu University)
138th Annual Meeting of the Pharmaceutical Society of Japan, Kanazawa, March 25-28, 2018.
Our findings on the functional effects of royal jelly
〇 Yukio Narita and Kenji Ichihara
API Company Limited
2018.3.22-26 16th German Apitherapy Congress (Passau, Germany)
Quantitative analysis of the higher-order structural protein, Apisin, in royal jelly Taichi Mitsui (API Co., Ltd.)
7th Annual symposium of Structural biology, medicine, and logical drug discovery research, Gifu, March 22, 2018.
Chemical constituents of Brazilian propolis from the state of Bahia and their growth inhibitory activities against cancer cells 〇Taichi Mitsui, Sho Hotta, Shigemi Tazawa, Kenji Kato, Kenji Ichihara (API Co., Ltd.)
Annual meeting of the Agricultural Chemical Society of Japan, Nagoya, March 15-18, 2018.
Neuroprotective activity of green Brazilian propolis in the murine hippocampal cell line HT22 〇Madoka Takashima 1,2, Kenji Ichihara 1, Yoko Hirata 2 (1API Co., Ltd., 2Gifu University)
Chemical constituents of Brazilian propolis from the state of Bahia and their growth inhibitory activities against cancer cells 〇Taichi Mitsui, Sho Hotta, Shigemi Tazawa, Kenji Kato, Kenji Ichihara (API Co., Ltd.)
Multivariate data analysis and functional evaluation of various honeys from different floral nectar resources 〇Yasuko Arai, Tomomi Morimoto, Saori Uehara, Kenji Kato, Kenji Ichihara (API Co., Ltd.)
8th Gifu Pharmaceutical University Lectures on Functional Health Foods, Gifu, November 25, 2017.
In vitro studies of Brazilian red propolis on allergen-induced degranulation and leukotriene B4 release 〇Saori Uehara, Tomomi Morimoto, Yasuko Arai, Taichi Mitsui, Yukio Narita, Kenji Ichihara (API Co., Ltd.)
Laboratory studies on the antidepressant-like effect of royal jelly
〇Noriyuki Iegaki 1, Yukio Narita 1, Noriko Hattori 1, Yoko Hirata 2, Kenji Ichihara 1
(1API Co., Ltd., 2Gifu University)
Annual meeting of the Agricultural Chemical Society of Japan, Kyoto, March 18-19, 2017.
Patents
(Under Construction.)